Interferon can inhibit the growth of certain tumors and tumor viruses. However, the efficacy of interferon treatment in cancer chemotherapy depends on the sensitivity of the tumor cell population to the inhibitory action of interferon. This sensitivity may be decreased by the presence of interferon antagonists in the oncogenic tissue. Interferon antagonists have been detected in natural embryonic tissues, in certain virus-infected cells and certain tumors. The overall goals of this research program are to determine if interferon antagonists are commonly present in certain tumors, to characterize the mode of action of interferon antagonists, and to develop methods to counteract their action. Sensitive quantitative methods to detect the presence of antagonists of chicken and mouse interferon have been developed. Studies to date indicate that natural embryonic interferon antagonists exist in young (6 day old) chicken embryos and in human placentas. The presence of interferon antagonist activity in 6 day chicken embryos indicates that interferon antagonists may be partially responsible for the limited sensitivity of 6 day chicken embryo cells to the action of interferon. The decrease in antagonist activity with embryonic development appears to parallel the increase in sensitivity to interferon of chicken embryo cells. The action of these natural embryonic antagonists is not species specific--they both inhibit the action of mouse and chicken interferon. The slopes of dose response curves of interferon alone and of interferon plus antagonists are not significantly different. This indicates the possibility that both interferon and the interferon antagonists may act at the same site. Currently, studies are being undertaken to characterize the mode of action of the embryonic antagonists, and to detect the presence of antagonists in various mouse and human tumors.